DESCRIPTION: Experimental allergic encephalomyelitis (EAE), an in vivo manifestation of the T lymphocyte immune response against myelin basic protein (MBP), has been the subject of intense study for many years. Although much has been learned about the interactions of antigen-presenting cells with immunodominant epitopes of MBP and the interaction of antigen-presenting cells with MBP-specific T-cells in vitro, the pathogenic processes that lead to clinical disease in vivo remain to be elucidated. The dynamics of the central nervous system (CNS) T-cell population during acute and relapsing EAE is an important aspect of this disease, particularly with respect to the design of immunotherapeutic protocols. An important question is whether the same T- cells are responsible for relapses as well as acute disease. The role of non-MBP-specific T-cells in the disease process needs clarification. Thus, the overall goal of this application is to analyze the role of antigen-specific and non-specific T-cell populations during the course of passively-induced acute and chronic relapsing EAE. The hypothesis that the episodic nature of murine EAE is due to sequential emergence of unique sets of neuroantigen epitope- specific T-cells in the CNS will be tested by passive transfer of neuroantigen peptide-specific T-cells to SJL rag-/-mutant mice lacking T-cells and B-cells. The course of EAE in the mutant mice will be indicative of the requirement for host non-neuroantigen-specific lymphoid cells for recovery and relapse. CNS T-cells from mice with acute and relapsing EAE will be assessed for V-beta families with V-beta specific monoclonal antibodies. Spectrotypic analysis will be used to assess heterogeneity of the TCR CDR3 region within V-beta families. Thus, the specific aims of this application are 1) To employ lymphoid cell deficient mice to assess the role of MBP peptide- specific T-cells in the course of chronic, relapsing EAE, 2) To test the hypothesis that determinant spreading as a result of secondary sensitization of peripheral T-cells plays a critical role in chronic, relapsing EAE, 3) To characterize T-cells in the spleen and CNS of the mutant mice with respect to V-beta family and spectrotype during the course of chronic relapsing disease.